SynthesisPLoS computational biology2022
Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention.
Synthesis in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, VRC07-523LS, and PGT121.414.LS infused intravenously or subcutaneously (HVTN 140/HPTN 101 part B): a phase 1, randomised trial.The lancet. HIV · 2026Trial
- VRC01 with antiretroviral initiation in infants is well tolerated, and higher concentrations associate with greater HIV-1 DNA declines.Science translational medicine · 2026Trial
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- Modeling quantifies in vivo neutralization, Fc-mediated killing, and resistance in human clinical trials of five anti-HIV broadly neutralizing antibodies.bioRxiv : the preprint server for biology · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Distinct modes of evolution drive HIV escape from two broadly neutralizing antibodies.bioRxiv : the preprint server for biology · 2025Article
- Dose finding in early-phase human immunodeficiency virus type 1 prevention monoclonal antibody clinical trials.Clinical trials (London, England) · 2025Review
- Immunogenicity of monkeypox virus surface proteins and cross-reactive antibody responses in vaccinated and infected individuals: implications for vaccine and therapeutic development.Infectious diseases of poverty · 2025Article
- Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.BMC immunology · 2025Article
- Defining criteria for broadly neutralizing HIV antibodies.Frontiers in immunology · 2025Review
- Review
- A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.Nature communications · 2024Article
- Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.Clinical microbiology reviews · 2024Review
- The potential of broadly neutralizing antibodies for HIV prevention.Journal of the International AIDS Society · 2024Article
- Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.Pharmaceutics · 2024Article
- A unifying model to explain high nirmatrelvir therapeutic efficacy against SARS-CoV-2, despite low post-exposure prophylaxis efficacy and frequent viral rebound.medRxiv : the preprint server for health sciences · 2024Article
- Article
- High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Broadly neutralizing antibodies (bNAbs) are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As with ART, bNAb combinations are likely needed to cover HIV's extensive diversity. Not all bNAbs are identical in terms of their breadth, potency, and in vivo longevity (half-life). Given these differences, it is important to optimally select the composition, or dose ratio, of combination bNAb therapies for future clinical studies. We developed a model that synthesizes 1) pharmacokinetics, 2) potency against a wide HIV diversity, 3) interaction models for how drugs work together, and 4) correlates that translate in vitro potency to clinical protection. We found optimization requires drug-specific balances between potency, longevity, and interaction type. As an example, tradeoffs between longevity and potency are shown by comparing a combination therapy to a bi-specific antibody (a single protein merging both bNAbs) that takes the better potency but the worse longevity of the two components. Then, we illustrate a realistic dose ratio optimization of a triple combination of VRC07, 3BNC117, and 10-1074 bNAbs. We apply protection estimates derived from both a non-human primate (NHP) challenge study meta-analysis and the human antibody mediated prevention (AMP) trials. In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.